title: Blood-based detection of radiation exposure in humans based on novel phospho-Smc1 ELISA.
abstract: The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kinase. In this study, we describe the generation of two novel ELISAs for quantifying phospho-Smc1(Ser-957) and phospho-Smc1(Ser-966). Using these novel assays, we quantify the kinetic and biodosimetric responses of human cells of hematological origin, including immortalized cells, as well as both quiescent and cycling primary human PBMC. Additionally, we demonstrate a robust in vivo response for phospho-Smc1(Ser-957) and phospho-Smc1(Ser-966) in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to (131)I. These assays are useful for quantifying the DNA damage response in experimental systems and potentially for the identification of individuals exposed to radiation after a radiological incident.
authors.affiliation: Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, Washington 98109-1024, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ivey
authors.forename: Heather D
authors.initials: HD
authors.lastname: Moore
authors.forename: Uliana J
authors.initials: UJ
authors.lastname: Voytovich
authors.forename: Cortlandt P
authors.initials: CP
authors.lastname: Thienes
authors.forename: Travis D
authors.initials: TD
authors.lastname: Lorentzen
authors.forename: Era L
authors.initials: EL
authors.lastname: Pogosova-Agadjanyan
authors.forename: Shani
authors.initials: S
authors.lastname: Frayo
authors.forename: Venissa K
authors.initials: VK
authors.lastname: Izaguirre
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Lundberg
authors.forename: Lacey
authors.initials: L
authors.lastname: Hedin
authors.forename: Kas Ray
authors.initials: KR
authors.lastname: Badiozamani
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Paulovich
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D064007:Ataxia Telangiectasia Mutated Proteins; D001774:Blood Chemical Analysis / Q000379:methods*; D018797:Cell Cycle Proteins / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D002868:Chromosomal Proteins, Non-Histone / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000172:deficiency; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010750:Phosphoproteins / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency; D011817:Rabbits; D011874:Radiometry / Q000379:methods*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000172:deficiency; D014916:Whole-Body Irradiation / Q000009:adverse effects; D055815:Young Adult; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D000911:Antibodies, Monoclonal; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010750:Phosphoproteins; D025521:Tumor Suppressor Proteins; D000098550:Structural Maintenance of Chromosome Protein 1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases